Biodistribution of therapeutic extracellular vesicles.

The field of extracellular vesicles (EVs) has seen a tremendous paradigm shift in the past two decades, from being regarded as cellular waste bags to being considered essential mediators in intercellular communication. Their unique ability to transfer macromolecules across cells and biological barriers has made them a rising star in drug delivery. Mounting evidence suggests that EVs can be explored as efficient drug delivery vehicles for a range of therapeutic macromolecules.

Establishing Human Observer Criterion in Evaluating Artificial Social Intelligence Agents in a Search and Rescue Task.

Artificial social intelligence (ASI) agents have great potential to aid the success of individuals, human-human teams, and human-artificial intelligence teams. To develop helpful ASI agents, we created an urban search and rescue task environment in Minecraft to evaluate ASI agents' ability to infer participants' knowledge training conditions and predict participants' next victim type to be rescued. We evaluated ASI agents' capabilities in three ways: (a) comparison to ground truth-the actual knowledge training condition and participant actions; (b) comparison among different ASI agents; and (c) comparison to a human observer criterion, whose accuracy served as a reference point.

Tumor-targeted glycogen nanoparticles loaded with hemin and glucose oxidase to promote tumor synergistic therapy.

Strategies which are used to address the low levels of intracellular hydrogen peroxide and the development of biocompatible catalysts still need to be fulfilled in tumor chemodynamic therapy. Therefore, a novel tumor-targeted glycogen-based nanoparticle system (GN/He/GOx/HA) was developed to co-deliver hemin (He) and GOx, which can self-supply glucose formed upon degradation of glycogen by α-glycosidase in the lysosome environment, in order to achieve synergistic antitumor therapy. Hyaluronic acid (HA) was selected as the outer shell to protect the activity of GOx, and to increase the uptake by tumor cells via CD44 receptor-mediated endocytosis.

I Can't See That! Considering the Readability of Small Objects in Virtual Environments.

Though virtual reality has repeatedly seen usability improvements through higher fidelity headsets, interacting with small objects has remained an issue due to a reduction in visual acuity. Given the current uptake of virtual reality platforms and the range of real world applications that they may be used for, it is worth considering how such interactions can be accounted for. We propose three techniques for improving the usability of small objects in virtual environments: i) expanding them in place, ii) showing a zoomed-in twin above the original object, and iii) showing a large readout of the object's current state.

Potential of 3-octanone as a lure and kill agent for control of the Brown garden snail.

The brown garden snail (Cornu aspersum) is a major agricultural pest, causing damage to a wide range of economically important crops. Withdrawal or restricted use of pollutant molluscicides like metaldehyde has prompted a search for more benign control products. This study investigated the response of snails to 3-octanone; a volatile organic compound (VOCs) produced by the insect pathogenic fungus Metarhizium brunneum.

Reference genomes of channel catfish and blue catfish reveal multiple pericentric chromosome inversions.

Background: Channel catfish and blue catfish are the most important aquacultured species in the USA. The species do not readily intermate naturally but F hybrids can be produced through artificial spawning. F hybrids produced by mating channel catfish female with blue catfish male exhibit heterosis and provide an ideal system to study reproductive isolation and hybrid vigor.

Sex differences in associations between APOE ε2 and longitudinal cognitive decline.

Introduction: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples.

Methods: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs.

What are the digitally enabled psychosocial interventions delivered by trained practitioners being offered to adults with life-shortening illnesses and palliative care needs and their informal and professional caregivers? A scoping review.

Objectives: Computer-mediated and telephone communication connecting professionals and patients (eHealth) is well established. Yet there is little information about psychosocial interventions delivered by trained practitioners for a palliative care population. The aim is to describe digitally enabled psychosocial interventions offered to adults with life-shortening or terminal illnesses and carers/families receiving palliative care, and how these are delivered and evaluated.

Machine learned interatomic potential for dispersion strengthened plasma facing components.

Tungsten (W) is a material of choice for the divertor material due to its high melting temperature, thermal conductivity, and sputtering threshold. However, W has a very high brittle-to-ductile transition temperature, and at fusion reactor temperatures (≥1000 K), it may undergo recrystallization and grain growth. Dispersion-strengthening W with zirconium carbide (ZrC) can improve ductility and limit grain growth, but much of the effects of the dispersoids on microstructural evolution and thermomechanical properties at high temperatures are still unknown.

Engineering olivocochlear inhibition to reduce acoustic trauma.

Efferent brain-stem neurons release acetylcholine to desensitize cochlear hair cells and can protect the inner ear from acoustic trauma. That protection is absent from knockout mice lacking efferent inhibition and is stronger in mice with a gain-of-function point mutation of the hair cell-specific nicotinic acetylcholine receptor. The present work uses viral transduction of gain-of-function receptors to restore acoustic prophylaxis to the knockout mice.

The Association Between Central Line-Associated Bloodstream Infection and Central Line Access.

Objectives: Identifying modifiable risk factors associated with central line-associated bloodstream infections (CLABSIs) may lead to modifications to central line (CL) management. We hypothesize that the number of CL accesses per day is associated with an increased risk for CLABSI and that a significant fraction of CL access may be substituted with non-CL routes.

Design: We conducted a retrospective cohort study of patients with at least one CL device day from January 1, 2015, to December 31, 2019.

Comparison of different methods for isolating CD8 T lymphocyte-derived extracellular vesicles and supramolecular attack particles.

CD8 T lymphocytes play vital roles in killing infected or deranged host cells, recruiting innate immune cells, and regulating other aspects of immune responses. Like any other cell, CD8 T cells also produce extracellular particles. These include extracellular vesicles (EVs) and non-vesicular extracellular particles (NVEPs).

Resident Education and Virtual Medicine: A Faculty Development Session to Enhance Trainee Skills in the Realm of Telemedicine.

Introduction: COVID-19 accelerated the use of telemedicine. Subsequently, clinical sites began conducting virtual visits. Academic institutions implemented telemedicine for patient care and simultaneously had to teach residents the logistics and best practices.

Incidence of transaminitis in adults with cystic fibrosis taking elexacaftor/tezacaftor/ivacaftor.

Background: Cystic fibrosis (CF) transmembrane conductance regulator modulators are a cornerstone of CF treatment. However, many patients develop CF liver disease (CFLD) over time, and previous data indicate a risk for transaminase elevation with modulator use. Elexacaftor/tezacaftor/ivacaftor is a commonly prescribed modulator with broad efficacy among CF genomic profiles.

Investigating Eukaryotic Elongation Factor 2 Kinase/Eukaryotic Translation Elongation Factor 2 Pathway Regulation and Its Role in Protein Synthesis Impairment during Disuse-Induced Skeletal Muscle Atrophy.

The principal mechanism underlying the reduced rate of protein synthesis in atrophied skeletal muscle is largely unknown. Eukaryotic elongation factor 2 kinase (eEF2k) impairs the ability of eukaryotic translation elongation factor 2 (eEF2) to bind to the ribosome via T56 phosphorylation. Perturbations in the eEF2k/eEF2 pathway during various stages of disuse muscle atrophy have been investigated utilizing a rat hind limb suspension (HS) model.

A Hybrid Stainless-Steel SPME Microneedle Electrode Sensor for Dual Electrochemical and GC-MS Analysis.

A mechanically robust in-tube stainless steel microneedle solid phase microextraction (SPME) platform for dual electrochemical and chromatographic detection has been demonstrated. The SPME microneedle was fabricated by layer-by-layer (LbL) in-tube coating, consisting of carbon nanotube (CNT)/cellulose nanocrystal (CNC) film layered with an electrically conductive polyaniline (PANI) hydrogel layer (PANI@CNT/CNC SPME microneedle (MN)). The PANI@CNT/CNC SPME MN showed effective analysis of caffeine by GC-MS with an LOD of 26 mg/L and excellent precision across the dynamic range.

A Trem2 mouse model without cryptic splicing drives age- and disease-dependent tissue damage and synaptic loss in response to plaques.

Background: The TREM2 R47H variant is one of the strongest genetic risk factors for late-onset Alzheimer's Disease (AD). Unfortunately, many current Trem2 mouse models are associated with cryptic mRNA splicing of the mutant allele that produces a confounding reduction in protein product. To overcome this issue, we developed the Trem2 (Normal Splice Site) mouse model in which the Trem2 allele is expressed at a similar level to the wild-type Trem2 allele without evidence of cryptic splicing products.

Application of Antisense Conjugates for the Treatment of Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1) is one of the most common muscular dystrophies and can be potentially treated with antisense therapy decreasing mutant DMPK, targeting miRNAs or their binding sites or via a blocking mechanism for MBNL1 displacement from the repeats. Unconjugated antisense molecules are able to correct the disease phenotype in mouse models, but they show poor muscle penetration upon systemic delivery in DM1 patients. In order to overcome this challenge, research has focused on the improvement of the therapeutic window and biodistribution of antisense therapy using bioconjugation to lipids, cell penetrating peptides or antibodies.

Effect of Anionic Lipids on Mammalian Plasma Cell Membrane Properties.

The effect of lipid composition on models of the inner leaflet of mammalian cell membranes has been investigated. Grazing incidence X-ray diffraction and X-ray and neutron reflectivity have been used to characterize lipid packing and solvation, while electrochemical and infrared spectroscopic methods have been employed to probe phase behavior in an applied electric field. Introducing a small quantity of the anionic lipid dimyristoylphosphatidylserine (DMPS) into bilayers of zwitterionic dimyristoylphosphatidylethanolamine (DMPE) results in a significant change in the bilayer response to an applied field: the tilt of the hydrocarbon chains increases before returning to the original tilt angle on detachment of the bilayer.

Development is in the details: Event-related theta oscillations reveal children and adults verify multiplication facts differently.

When verifying the correctness of single-digit multiplication problems, children and adults show a robust ERP correctness effect thought to reflect similar cognitive processes across groups. Recent studies suggest that this effect is instead a modulation of the negative-going N400 component in children, reflecting access to semantic memory, and the positive-going P300 component in adults, reflecting stimulus categorization. However, the relative difference in ERP amplitude is the same for both components, more positive for correct than incorrect solutions, presenting a challenge to ascertaining the appropriate interpretation.

Response to Preoperative Dexamethasone Predicts Postoperative Neurological Improvement of Focal Neurological Deficits in Patients With Brain Metastases.

Background: Steroids are used ubiquitously in the preoperative management of patients with brain tumor. The rate of improvement in focal deficits with steroids and the prognostic value of such a response are not known.

Objective: To determine the rate at which focal neurological deficits respond to preoperative corticosteroids in patients with brain metastases and whether such an improvement could predict long-term recovery of neurological function after surgery.